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Biomedical subjects

M Plaut

Publications and source records attributed to M Plaut.

At least 55 records · Page 3Linked to original sources
PubMed1982

H2 antihistamines augment antigen-induced histamine release from human basophils in vitro.

H2 antihistamines, including cimetidine, burimamide, metiamide, and tiotidine, consistently augmented antigen-induced histamine release from human basophils in vitro when control histamine release was less than 20% of total. This effect was specific to the H2-receptor blocking activity of these drugs: equivalent degrees of receptor blockade by four different H2 antihistamines resulted in equipotent enhancement; H1-receptor antagonists did not alter histamine release; and aminoguanidine and amodiaquine, agents that inhibit histamine metabolism but do not block H2 receptors, did not enhance histamine release. Cimetidine did not enhance release when present a) when basophils were "activated" but did not release histamine ("first stage"), or b) when basophils were no longer susceptible to histamine inhibition ("second stage"). Thus, H2 antagonists enhanced histamine release by blocking the capacity of released histamine to act on H2 receptors to inhibit release. Because it is likely that only small percentages of histamine are released in vivo, it is possible that H2 antihistamines amplify the inflammatory process by blocking the inhibitory effects of the released histamine.

Amodiaquine↗
PubMed1981

Increased responsiveness to adenosine 3'5'-cyclic monophosphate-active agents during the immune response in vivo.

Cytotoxic T lymphocytes (CTL) were generated in the spleen following immunization of C57BL/6 mice with allogeneic cells. The activity of such CTL was inhibited by agents that increased intracellular adenosine 3'5',-cyclic monophosphate (cAMP) levels. During the primary immune response, the susceptibility of CTL to inhibition by theophylline remained constant, but susceptibility to histamine, prostaglandin E2 (PGE2). dibutyryl cAMP, and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro-20-1724) increased significantly. The pattern of increased inhibition by histamine differed from that of the other agents. Increased cAMP responsiveness of CTL resulted from at least two distinct biochemical events, possibly including 1) increased receptors and/or increased receptor-adenylate cyclase coupling (for histamine); and 2) increased efficiency of a post cAMP pathway (for dibutyryl cAMP, PGE2, and Ro 20-1724).

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1980

Hydrocortisone and human lymphocytes: increases in cyclic adenosine 3':5'-monophosphate and potentiation of adenylate cyclase-activating agents.

We have investigated the effect of hydrocortisone on the cyclic adenosine 3':5'-monophosphate (cAMP) response of human lymphocytes and polymorphonuclear leukocytes. Hydrocortisone (10(-6)-10(-3)M) caused a dose-dependent increase in the cAMP content of human lymphocytes which occurred rapidly (within 1 min); the cAMP level peaked at about 10 min, remained elevated for 90 min and decreased promptly to base line if the cells were washed free of hydrocortisone. In contrast to its effects on lymphocytes, hydrocortisone caused only a small dose-dependent increase in cAMP content of polymorphonuclear leukocytes which became significant only at high concentrations. In addition to increasing lymphocyte cAMP levels, hydrocortisone (10(-6)-10(-3)M) markedly potentiated the effect of many adenylate cyclase-stimulating agents including beta adrenergic stimuli, histamine, adenosine, prostaglandin E1 and cholera enterotoxin. The biochemical mechanism(s) of these actions of hydrocortisone were explored and it was found that hydrocortisone exerted its effects neither by blocking extracellular cAMP efflux, nor by inducing protein synthesis, nor by activating prostaglandin metabolic pathways, nor by preventing receptor (e.g., beta adrenergic receptor) desensitization. Hydrocortisone probably does not work as a cAMP phosphodiesterase inhibitor, since it did not inhibit lymphocyte phosphodiesterase, and the magnitude of synergistic potentiation by hydrocortisone was greater than that of potent phosphodiesterase inhibitors. Thus, hydrocortisone might act on the adenylate cyclase enzyme system by other, unknown mechanism(s). The ability of hydrocortisone to increase cAMP and especially to potentiate adenylate cyclase-stimulating agonists may partly explain the potent in vivo anti-inflammatory effect of corticosteroids in man.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Effect of solvent on the histamine-releasing, enzyme-releasing, and mitogenic properties of the calcium ionophore A23187.

The potency of the calcium ionophore A23187 in inducing three activities of human leukocytes (histamine secretion from basophils, enzyme secretion from PMNs, and proliferation of lymphocytes) was markedly dependent on the solvent (DMSO versus ethanol versus aqueous buffer) used for its initial sonication. While 0.1 micrograms/ml of DMSO- and ethanol-solubilized A23187 induced maximal histamine release from basophils and histaminase release from PMNs, concentrations of aqueous buffer-sonicated ionophore of greater than or equal to 1 microgram/ml were required for an equivalent response. Ionophore sonicated in organic solvents caused a maximum release of 40% of PMN beta-glucuronidase, at an optimal concentration tenfold higher than that required for maximal histaminase release; ionophore sonicated in aqueous buffers, even at high concentrations, effected a release of less than 5% of cellular beta-glucuronidase. A23187 also induced lymphocyte proliferation over a narrow concentration range; 0.05 micrograms/l of DMSO-sonicated ionophore induced optimal proliferation and concentrations greater than or equal to 0.2 micrograms/ml were toxic. Twofold higher concentrations of ethanol-sonicated ionophore and fourfold higher concentrations of aqueous-sonicated ionophore were necessary for maximal proliferation, and the magnitude of the maximal response with aqueous-sonicated A23187 was only one-half that of DMSO-solubilized agent. Ionophore-induced release of histamine from basophils and enzymes from PMNs was not cytotoxic, since ionophore induced neither LDH nor histamine release from heat-treated (47 degrees C) cells. These results explain several previous, discordant reports on the presence or absence of an effect of A23187 on cellular secretory events, on differing dose-response relationships, and on cytotoxic versus noncytotoxic mechanisms of action.

Anti-Bacterial Agents↗
PubMed1978

Characterization of a specific adenosine receptor on human lymphocytes.

We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 micrometer to 10 micrometer) increased lymphocytes cAMP levels in a dose-dependent fashion with a maximal (10 micrometer) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 micrometer. Adenosine appears to act on the cell surface since 1) 2-chloroadenosine, a poorly metabolized adenosine analogue, was as active as adenosine and 2) dipyridamole, which markedly inhibited [3H]-adenosine uptake by human lymphocytes, did not affect adenosine-induced accumulation of cAMP. The specificity of the adenosine effect was established by showing that the methylxanthine derivatives, theophylline and 3-isobutyl-1-methylxanthine (IBMX), specifically block the accumulation of cAMP in lymphocytes induced by adenosine. Theophylline is a competitive inhibitor of the effect of adenosine, with an estimated dissociation constant of theophylline-receptor complex of about 6.3 X 10(-7) M. The results suggest that adenosine increases the intracellular cAMP content of lymphocytes as a result of its interaction with a specific membrane receptor which results in the activation of adenylate cyclase.

Adenosine↗
PubMed1977

Selective display of histamine receptors on lymphocytes.

Histamine, acting on histamine type 2 receptors, increases intracellular cyclic adenosine monophosphate (AMP) and thus modulates the immunologic functions of lymphocytes. Lymphocyte cyclic AMP levels were used to follow the development of histamine receptors. The B lymphocytes have no functional histamine receptors. As T lymphocytes "mature" in immunologic function--from thymocytes to cortisone-resistant thymocytes to splenic T lymphocytes--their response to histamine increases. The response of these subpopulations of lymphocytes to isoproterenol is the inverse of the histamine response. It is suggested that the changing display of histamine receptors plays an important part in the control of immunologic responses.

Animals↗
PubMed1976

Studies of the mechanism of lymphocyte-mediated cytolysis. VII. Two stages in the T cell-mediated lytic cycle with distinct cation requirements.

The lysis of allogeneic cells by cytolytically active T lymphocytes has been shown to involve two stages, Each with distinct cation requirements. Cytolysis required the presence of Ca++ ions, but addition of Mg++ to Ca++ containing medium synergistically enhanced target cell destruction. This synergistic effect resulted form kinetically separable events mediated by these cations. Thus, optimal adhesions between killer and target cells necessitated the presence of Mg++; interactions also occurred, but less efficiently, in the presence of Ca++. Lymphocyte-target cell interactions resulting from the present of Mg++ did not lead to the lysis of the target cell, until Ca++ were added. A "late" stage of the establishment of a target cell lesion is thus uniquely served by Ca++.

Animals↗
PubMed1975

Properties of a subpopulation of T cells bearing histamine receptors.

C57BL/6 mice immunized i.p. with alloantigen (P815 mastocytoma cells) develop cytolytically active thymus-derived (T) splenic lymphocytes. The definition of specific histamine receptor sites on effector T cells has been studied by measuring the in vitro effects of the hormone on cytolytic activity. Histamine was found to inhibit cytolysis reversibly and to increase lymphoid cell cyclic AMP levels. Both of these histamine activities were reversed by burimamide and metiamide; neither activity was affected by diphenhydramine or pyrilamine. These findings indicate that modulation of effector T cell activity by histamine is mediated only by one of the subtypes of tissue histamine receptors, designated a histamine-type 2 receptor. This receptor appears to be present on cytolytically active cells; there is no evidence for activation by histamine of auxiliary or "suppressor" cells. The estimated dissociation constant (KB) for the burimamide-receptor complex (9 times 10-minus 6 tm) and for the metiamide-receptor complex (8 times 10-minus 7 M) indicated that the histamine receptor on T cells is quite similar to histamine-type 2 receptors in other tissues. Cells bearing such receptors could not be isolated by passage through a column of histamine-coated tsepharose beads. The cytolytic activity of spleen cells taken from mice early (days 7-9) after immunization is virtually unaffected by histamine in vitro. In contrast, the activity of spleen cells taken from mice later in the immune response is progressively more susceptible to inhibition by histamine. After reaching a maximum at day 11, the spleen cell cytolytic activity falls in a pattern that parallels the increase in susceptibility to histamine. The susceptibility of effector T cells to histamine appears also to reflect their site of origin, for peritoneal exudate effector cells were found to be significantly less sensitive than spleen cells to inhibition by histamine. The progressive increase in inhibition by histamine apparently reflects the appearance of greater numbers of specific histamine-type 2 receptors, and is probably a general phenomenon, for spleen cells from A/J or C3H mice immunized with either P815 mastocytoma (H-2d) or EL-4 (H-2b) cells showed the same effect. However, the appearance of histamine receptors could be altered by prior immunization with an unrelated alloantigen: thus, when A/J mice are preimmunized with EL-4, a subsequent immunization with mastocytoma cells results in peak spleen anti-H-2d activity at day 9 instead of days 11-13, and the appearance of significant (greater than 40 percent) inhibition by histamine as early as day 8 instead of day 16. The physiological role of the histamine receptors is as yet undefined, though their unexpected rate of appearance on effector T cells, coincident with a decline in the number of lytically active cells in vivo, may be a significant hint that hormone receptors play a role in the control of T-cell proliferation.

Animals↗